During the past several years we have been able to breed an inborn strain of rats which, after being fed a diet high in sucrose, develops a syndrome close to that found in human diabetes mellitus including renal and retinal microangiopathy. The objectives of the present project are to study in vivo the involvement of collagen in this diabetic syndrome, either by being primarily affected due to genetic abberations, or as a secondary consequence of the metabolic changes. The experiments will include: 1) genetically susceptible animals which develop diabetes when fed a sucrose rich diet and their starch-fed-non-diabetic controls; 2) genetically resistant animals which do not develop diabetes following a sucrose rich diet; 3) normal, regularly fed animals. The development of the syndrome will be followed by testing blood glucose levels after an oral glucose load, plasma insulin levels after a glucose load, activities of liver enzymes associated with glycolysis, gluconeogenesis and lipogenesis, blood lipids and histological changes in the heart, aorta, retina and kidney. The tests will be carried out further 2, 4, 6, and 8 months after the onset of diabetes. To study the effect of the diabets on synthesis in vivo of the different collagen types, a pulse label of 3H-proline will be injected i.p. 6, 12, or 24 hours before sacrifice at each time point and the specific radioactivity of hydroxyproline will be determined in skin, cartilage, tendon, retina, heart, aorta and kidney. Collagen crosslinking, will be studied in vivo using both the diffusion chamber technique and lysyl oxidase assay. Hydroxyproline excretion in the urine and its specific radioactivity will indicate collagen degradation in the various animal groups. The data obtained from the collagen studies will be correlated with those obtained from the biochemical and histopathological examinations as mentioned above.